Effects of 14 frequently used drugs on prostate-specific antigen expression in prostate cancer LNCaP cells

Abstract

Prostate cancer occurs more frequently among older males and such elderly individuals often have chronic underlying disorders for which various drugs are administered for treatment. The levels of prostate-specific antigen (PSA), a widely used prostate cancer marker, are influenced by a number of drugs, such as non-steroidal anti-inflammatory drugs and statins. In the present study, the drugs prescribed to patients on a repeat prescription collected at the pharmacy of the Gifu Pharmaceutical University (Gifu, Japan) were examined for their effects on the levels of PSA expression in prostate cancer LNCaP cells. Among the 14 drugs investigated, betamethasone, an agonist of the glucocorticoid receptor, was found to increase the levels of PSA mRNA expression in the LNCaP cells. This betamethasone-induced expression was mediated, at least in part, through androgen receptor (AR) transcriptional activation. Dexamethasone, a typical agonist of the glucocorticoid receptor, was also found to stimulate the AR transcriptional activity, however, to a lesser extent than betamethasone. Therefore, it would be interesting to examine in future studies whether the serum PSA levels in prostate cancer patients are influenced by betamethasone.

Keywords: LNCaP; betamethasone; prostate-specific antigen.

Figure 1

Effects of various drugs on the viability of prostate cancer LNCaP cells. LNCaP cells were treated with various drugs for three days and cell viability was determined by the alamarBlue assay. Data are presented as the mean ± standard deviation of four different incubations. ^*P<0.05 and ^**P<0.01 vs. control.

Figure 2

Effect of various drugs on the level of PSA mRNA expression in LNCaP cells. LNCaP cells were treated with 20 μM of each drug for three days with the exception of amlodipine and lansoprazole, which were administered at 2 and 5 μM, respectively. Following incubation, total RNA was isolated and subjected to real-time reverse transcription-polymerase chain reaction analysis. The results were normalized to β-actin (ACTB) levels (n=4). ^**P<0.01 vs. control. The dashed line represents the baseline control (no drug). PSA, prostate-specific antigen.

Figure 3

Effects of betamethasone and dexamethasone on the levels of PSA mRNA expression and androgen receptor transcriptional activity in LNCaP cells. LNCaP cells were seeded in phenol red-free RPMI-1640 medium with 2% charcoal stripped fetal bovine serum. (A) Cells were treated with 1–20 μM betamethasone or dexamethasone for three days, after which the total RNA was isolated and subjected to real-time reverse transcription-polymerase chain reaction analysis. The results were normalized to β-actin (ACTB) levels (n=4). ^**P<0.01 vs. control. (B) Following 24 h, the cells were transfected with the MMTV-luc and phRL-TK vectors and treated with 0.1–20 μM betamethasone or dexamethasone for a further 24 h. The cell lysates were prepared and firefly luciferase activity was measured using the Luciferase Reporter assay system and normalized to Renilla luciferase activity. ^**P<0.01 and ^***P<0.001 vs 0 μM. PSA, prostate-specific antigen.